Icariin

Icariin (Ieariline) is a major constituent of flavonoids from the Chinese medicinal herb Epimedium brevicornum; exhibits multiple biological properties, including anti-inflammatory, neuroregulatory and neuroprotective activities. (In Vitro) :Icariin is a cGMP-specific PDE5 inhibitor. The inhibitory effects of Icariin on PDE5 and PDE4 activities are investigated by the two-step radioisotope procedure with 3H-cGMP/3H-cAMP. The potency of selectivity of Icariin on PDE5 (PDE4/PDE5 of IC50) is 167.67 times. Cell viability is measured in the present study to evaluate whether Icariin protect endothelial HUVECs from injuries induced by oxidized low-density lipoprotein (ox-LDL) . The exposure of the cells to ox-LDL for 24 h significantly decreases the cell viability compared with control group (P<0.05) . However, Icariin can inhibit cell injury induced by ox-LDL in a concentration-dependent manner, and has significant difference (P<0.05) compared with ox-LDL-simulated group.Icariin protects BMSCs against OGD-induced apoptosis by inhibiting ERs-mediated (ER Stress) autophagy via MAPK signaling pathway. (In Vivo) :Icariin is a PPARα activator, induces Cyp4a10 and Cyp4a14, and regulates the mRNA levels of lipid metabolism enzymes and proteins, including fatty acid binding protein, fatty acid oxidation in mitochondria and in peroxisome. Icariin is effective in the treatment of hyperlipidemia. To understand the effect of Icariin on lipid metabolism, effects of Icariin on PPARα and its target genes are investigated. Mice are treated orally with Icariin at doses of 0, 100, 200, and 400 mg/kg, or Clofibrate (500 mg/kg) for five days. Liver total RNA is isolated and the expressions of PPARα and lipid metabolism genes are examined. PPARα and its marker genes Cyp4a10 and Cyp4a14 are induced 2-4 fold by Icariin, and 4-8 fold by Clofibrate. The fatty acid (FA) binding and co-activator proteins Fabp1, Fabp4 and Acsl1 are increased 2-fold. The mRNAs of mitochondrial FA β-oxidation enzymes (Cpt1a, Acat1, Acad1 and Hmgcs2) are increased 2-3 fold. The mRNAs of proximal β-oxidation enzymes (Acox1, Ech1, and Ehhadh) are also increased by Icariin and Clofibrate. The expression of mRNAs for sterol regulatory element-binding factor-1 (Srebf1) and FA synthetase (Fasn) are unaltered by Icariin. The lipid lysis genes Lipe and Pnpla2 are increased by Icariin and Clofibrate. Adult rats are treated orally with Icariin at doses of 0 (control), 50, 100, or 200 mg/kg body weight for 35 consecutive days. The results show that Icariin has virtually no effect on the body weight or organ coefficients of the testes or epididymides. However, 100 mg/kg Icariin significantly increases epididymal sperm counts. In addition, 50 and 100 mg/kg Icariin significantly increase testosterone levels. Furthermore, 100 mg/kg Icariin treatment also affects follicle stimulating hormone receptor (FSHR) and claudin-11 mRNA expression in Sertoli cells. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels are measured in the testes; 50 and 100 mg/kg Icariin treatment improve antioxidative capacity, while 200 mg/kg Icariin treatment upregulates oxidative stress.